Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy Journal Article
| Authors: | Boardman, A. P.; Gutgarts, V.; Flynn, J. R.; Devlin, S. M.; Goldman, A.; Tomas, A. A.; Fein, J. A.; Slingerland, J. B.; Parascondola, A.; Lin, R. J.; Scordo, M.; Dahi, P. B.; Geralt, S. A.; Palomba, M. L.; Salles, G.; Nath, K.; Walji, M.; Corona, M.; Park, J. H.; Shah, G. L.; Perales, M. A.; Jaffer-Sathick, I.; Shouval, R. |
| Article Title: | Predictors and implications of renal injury after CD19 chimeric antigen receptor T-cell therapy |
| Abstract: | Chimeric antigen receptor (CAR) T cells targeting CD19 induce durable remissions in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), but many patients experience treatment-related toxicity. Cytokine release syndrome and immune effector cell-associated neurologic syndrome are extensively characterized. However, limited data exist on the burden, predictors, and implications of acute kidney injury (AKI) after CAR T-cell therapy. On initial screening of the Food and Drug Administration adverse event reporting system, we identified a disproportionately high rate of renal adverse events among nearly 6,000 CAR T adverse event reports, suggesting it is clinically important in this patient population. In a subsequent single-center analysis of 399 NHL patients treated with CD19 CAR T cells, we found a substantial burden of AKI after CAR T infusion (10% and 5% of any grade and grade ≥2 AKI) with pre-renal causes being predominant (72%). Evolution to chronic kidney disease was rare, however, three patients required hemodialysis. Importantly, patients experiencing cytokine release syndrome and/or neurotoxicity as well as those with low serum albumin and high inflammatory cytokines, including IL-6 and TNF-α, were more likely to develop AKI. While pre-CAR T renal dysfunction was not associated with adverse outcomes, patients developing post-CAR T AKI had lower overall survival compared to their counterparts. Our findings indicate that renal dysfunction is a common toxicity of CAR T-cell therapy with meaningful prognostic impact. Notably, the link between systemic inflammation and renal dysfunction, suggests that readily available biomarkers may inform on renal injury risk after CAR T-cell therapy. ©2025 Ferrata Storti Foundation. |
| Keywords: | adult; controlled study; aged; middle aged; overall survival; fludarabine; allogeneic stem cell transplantation; c reactive protein; interleukin 10; bendamustine; creatinine; cyclophosphamide; hemoglobin; acute kidney failure; hospitalization; immunology; albumin; karnofsky performance status; kidney injury; lymphoma, non-hodgkin; interleukin 6; chimeric antigen receptor; lactate dehydrogenase; hemodialysis; therapy; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; antigens, cd19; cd28 antigen; ferritin; fibrinogen; tumor necrosis factor; non-hodgkin lymphoma; etiology; adverse event; cytokine release syndrome; acute kidney injury; procedures; estimated glomerular filtration rate; humans; prognosis; human; male; female; article; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel; lisocabtagene maraleucel; receptors, chimeric antigen; brexucabtagene autoleucel |
| Journal Title: | Haematologica |
| Volume: | 110 |
| Issue: | 3 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2025-03-01 |
| Start Page: | 651 |
| End Page: | 664 |
| Language: | English |
| DOI: | 10.3324/haematol.2024.286021 |
| PUBMED: | 39568416 |
| PROVIDER: | scopus |
| PMCID: | PMC11873692 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Roni Shouval -- MSK author Sergio Giralt's last name is misspelled on the original publication -- Source: Scopus |
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